INTRACELLULAR IRON REGULATES IRON-ABSORPTION AND IRP ACTIVITY IN INTESTINAL EPITHELIAL (CACO-2) CELLS

In vertebrates, body Fe homeostasis is maintained through the regulati on of its intestinal absorption. In addition, because Fe is both essen tial and toxic, intracellular Fe levels are tightly regulated. Consequ ently, intestinal epithelial cells are in the unique position of being responsible simultaneously for the regulation of body Fe absorption a nd the regulation of their intracellular Fe levels to remain viable. W e tested the hypothesis that the regulation of transepithelial Fe tran sport and the regulation of intracellular Fe levels are sensitive to a common effector. To this end, we used a recently developed protocol t o obtain cultured intestinal epithelial cells with defined intracellul ar Fe concentrations. In these cells we tested Fe absorption and Fe re gulatory protein (IRP) activities. We found that transepithelial Fe tr ansport was inversely related to 20-200 mu M intracellular Fe and that Caco-2 cells expressed Fe regulatory protein-1 and Fe regulatory prot ein-2 activities. Fe regulatory protein-1 activity, Fe regulatory prot ein-2 mass, transferrin receptor density, and ferritin levels were reg ulated by intracellular Fe in the same range (20-200 mu M) that affect ed transepithelial Fe transport. These results suggest that a common F e-responsive factor regulates both intracellular Fe levels and Fe abso rption by Caco-2 cells.